Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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In a study on comparative metabolism of two S-triazines, [ 14 C]atrazine ([U 14 C]-triazine labeled;
radiochemical purity, 96.4–97.0%; purity of unlabeled atrazine, 97.5–98.9%) was given to female
Sprague-Dawley rats as a single oral dose at 1 or 76 mg/kg bw. Urine and faeces were collected at
24-h intervals for 3 days. At 72 h after treatment, the rats were killed and brains were analysed for
residual radioactivity. Within 72 h, approximately 69% of the radioactivity was eliminated in the
urine and approximately 16% in the faeces. Residues of atrazine equivalents in brain were 0.167 and
3.85 ppm for the lower and higher dose, respectively. No parent compound or its dealkylated metabolites
were found in brain. Sample of urine analysed by cation exchange chromatography, HPLC and
two-dimensional TLC showed that DACT (G 28273) was the major metabolite of atrazine, accounting
for approximately 24–29% of the administered dose in urine for 0–24 h, while another chloros-triazine
metabolite (metabolite UD, consisting of a mixture of chloro sidechain acids) accounted
for approximately 6% of the administered dose. The total of the mercapturate of atrazine (CGA-
359008) and the mercapturate metabolites (CGA-246059, CGA-63079 and CGA-10582) accounted
for approximately 2–3% of the administered dose (Simoneaux, 2001).
Monkeys
In a study described previously (section 1.1, Hui et al., 1996a), female Rhesus monkeys
received [ 14 C]atrazine intravenously as a single dose at 0.26 mg per monkey, and samples of urine,
faeces and blood were collected during 168 h after treatment. Atrazine metabolites identified in the
urine by TLC included 10.7% DEA (G 30033), 13.7% DIA (G 28279), 4.4% atrazine mercapturate
and 5.6% di-dealkylated atrazine mercapturate. Plasma contained trace amounts of atrazine in addition
to G 30033, G 28279 and G 28273. The mercapturic acid of atrazine, as determined by enzyme
immunoassay (EIA), was detected primarily in urine samples collected during the first 24 h after
dosing. All four potential mercapturic acid conjugates of chlorotriazine moieties were detected in the
urine using the LC/MS/MS method (liquid chromatography/mass spectroscopy). The total mercapturic
acid residues in 0–24 h composite urine samples ranged from 15 to 25 ppb and the individual mercapturic
acids ranged from 1 to 14 ppb. Total accountability of the mercapturates ranged from 1.6%
to 3.0% of the total radioactive residues (TRR). The amount of atrazine mercapturate (CGA 359008)
present in the composite sample as determined by EIA was an average of 16 times greater than the
amount determined by LC/MS/MS. Based upon preliminary characterization data, it was postulated
that one or more unknown chlorotriazine compounds altered in one of the side-chain alkyl groups
could react with the EIA reagent to explain the higher results obtained by this method compared with
the more specific LC/MS/MS method (Hui et al., 1996a).
In a study described previously (section 1.1, Hui et al., 1996b), female Rhesus monkeys
received [ 14 C]atrazine orally as a single dose at 1, 10 and 100 mg per monkey, and samples of urine,
faeces and blood were collected during 168 h after treatment. Samples of urine were analysed by
TLC and gas chromatography/mass selective detection (GC/MSD) for atrazine and its dealkylated
metabolites DEA (G 30033), DIA (G 28279), and DACT (G 28273). Both analytical methods gave
similar amounts of chlorotriazine residues. An average of approximately 11% of the administered
dose in all dose groups was found as chlorotriazine residues when measured in urine samples for
0–24 h, the major metabolites in urine were G 30033 and G 28273. Atrazine mercapturate (CGA
359008) accounted for 1% or less of the total radioactive residues in urine (Hui et al., 1996b).
Humans
In a study on kinetics and metabolism, six adult male volunteers received atrazine (purity not
reported) as a single oral dose of 0.1 mg/kg bw. Urine was collected over 168 h. Blood samples were
obtained from one man at 0, 2, 3, 4, 5, 6, 8, 24, 32, 72 and 168 h after dosing. Samples of urine and
blood were analysed for atrazine and its dealkylated metabolites DEA (G 30033), DIA (G 28279)
ATRAZINE 37–138 JMPR 2007